Áñez Germán, McGarry Alice, Woo Wayne, Kotloff Karen L, Gay Cynthia L, Zhu Mingzhu, Cloney-Clark Shane, Nelson Joy, Dunbar Haoua, Cai Miranda R, Cho Iksung, Cai Zhaohui, Kalkeri Raj, Plested Joyce S, Patel Nita, Smith Katherine, Marchese Anthony M, Glenn Gregory M, Mallory Raburn M, Dunkle Lisa M
Novavax, Inc., Gaithersburg, MD, USA.
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, USA.
Vaccine. 2025 Jun 5;61:127362. doi: 10.1016/j.vaccine.2025.127362.
BACKGROUND: NVX-CoV2373, a recombinant SARS-CoV-2 spike (rS) protein vaccine with Matrix-M® adjuvant, has been authorized for use in adults and adolescents. PREVENT-19 (NCT04611802/2019nCoV-301), a pivotal phase 3, randomized, placebo-controlled trial demonstrated robust efficacy of a primary, 2-dose series of NVX-CoV2373 against COVID-19. METHODS: Protocol expansions to PREVENT-19 included enrollment of adolescents (aged 12 to <18 years) and administration of 3rd and 4th doses of NVX-CoV2373 to adults and adolescents. Participants randomized 2:1 received NVX-CoV2373 or placebo 21 days apart; 3rd and 4th doses were administered ≥6 months after the preceding dose. Secondary and additional assessments included post-3rd- and 4th-dose immune responses (neutralizing antibody [nAb], anti-rS IgG, human angiotensin-converting enzyme-2-receptor binding inhibition [hACE2-RBI]) and response durability (post-3rd dose) to ancestral virus; cross-reactivity to Omicron subvariants; safety; and reactogenicity. RESULTS: Immune responses were observed against ancestral virus after two doses of NVX-CoV2373 but not after placebo. In both adults and adolescents, additional doses of NVX-CoV2373 increased nAb titers, anti-rS IgG levels, and hACE2-RBI; durable responses were recorded 8 months post 3rd dose. nAb responses post 3rd dose were noninferior to those post primary series. Cross-reactivity to BA.5 and BQ.1.1 variants was also observed, with anti-rS IgG levels post 3rd or 4th dose exceeding previously reported correlates of protection. Additional doses of NVX-CoV2373 were well tolerated, with no new safety signals. CONCLUSIONS: NVX-CoV2373 elicited robust and durable humoral immune responses to ancestral SARS-CoV-2 as a 3rd and 4th dose after the primary series in adults and adolescents. Cross-reactivity to relevant variants provides insight into potential protection against antigenically related, but shifted, viral strains. Additional doses of NVX-CoV2373 were well tolerated with no new safety signals. These results support the utility of this vaccine platform and continued updates, based on currently circulating strains, to help effectively combat SARS-CoV-2 infection.
背景：NVX-CoV2373是一种含Matrix-M®佐剂的重组严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（rS）蛋白疫苗，已被批准用于成人和青少年。PREVENT-19（NCT04611802/2019nCoV-301）是一项关键的3期、随机、安慰剂对照试验，证明了NVX-CoV2373的2剂基础免疫方案对新型冠状病毒肺炎（COVID-19）具有强大的疗效。 方法：PREVENT-19的方案扩展包括纳入青少年（12至<18岁），以及为成人和青少年接种第3剂和第4剂NVX-CoV2373。按2:1随机分组的参与者每隔21天接受一次NVX-CoV2373或安慰剂；第3剂和第4剂在前一剂之后≥6个月接种。次要和附加评估包括第3剂和第4剂接种后的免疫反应（中和抗体[nAb]、抗rS IgG、人血管紧张素转换酶2受体结合抑制[hACE2-RBI]）以及对原始病毒的反应持久性（第3剂接种后）；对奥密克戎亚变体的交叉反应性；安全性；以及反应原性。 结果：两剂NVX-CoV2373接种后可观察到针对原始病毒的免疫反应，而安慰剂接种后未观察到。在成人和青少年中，额外接种NVX-CoV2373均提高了nAb滴度、抗rS IgG水平和hACE2-RBI；在第3剂接种后8个月记录到持久反应。第3剂接种后的nAb反应不劣于基础免疫系列接种后。还观察到对BA.5和BQ.1.1变体的交叉反应性，第3剂或第4剂接种后的抗rS IgG水平超过了先前报道的保护相关水平。额外接种NVX-CoV2373耐受性良好，未发现新的安全信号。 结论：NVX-CoV2373作为成人和青少年基础免疫系列后的第3剂和第4剂，可引发针对原始SARS-CoV-2的强大且持久的体液免疫反应。对相关变体的交叉反应性为潜在预防抗原相关但发生变异的病毒株提供了见解。额外接种NVX-CoV2373耐受性良好，未发现新的安全信号。这些结果支持了该疫苗平台的实用性，并基于当前流行毒株持续更新，以帮助有效对抗SARS-CoV-2感染。
J Allergy Clin Immunol. 2025-6
Hum Vaccin Immunother. 2024-12-31
JMIR Public Health Surveill. 2024-10-16
Clin Infect Dis. 2024-7-19
MMWR Morb Mortal Wkly Rep. 2024-2-1
Vaccine. 2023-6-29
Zotero 插件